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临床试验/NCT02268409
NCT02268409已完成2 期

An Open-Label Extension Study To Evaluate The Long-Term Effects Of ACE-536 In Patients With β-Thalassemia Previously Enrolled In Study A536-04

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA1 个研究点 分布在 1 个国家目标入组 51 人开始时间: 2014年10月20日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
2 期
状态
已完成
发起方
入组人数
51
试验地点
1
主要终点
Number of Participants Who Experienced an Adverse Event (AE)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Study A536-06 (MK-6143-004) is an open-label extension study for participants previously enrolled in study A536-04 (NCT01749540), to evaluate the long-term safety and tolerability of luspatercept in adult participants with beta-thalassemia.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Completion of the treatment period in the base study A536-
  • •Females of child- bearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy, or are not naturally postmenopausal ≥24 consecutive months) must have negative urine or blood pregnancy test prior to enrollment and use adequate birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 12 weeks following the last dose of study drug
  • •Males must agree to use a latex condom during any sexual contact with females of child-bearing potential during study participation and for 12 weeks following the last dose of study drug, even if he has undergone a successful vasectomy
  • •Participants must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of study drug
  • •Participants with treatment interruption (defined as participants who complete the end of study visit for study A536-04 and are ≥28 days post end of study visit) must also meet the following criteria:
  • •Mean hemoglobin concentration <10.0 g/dL of 2 measurements (not influenced by red blood cell [RBC] transfusion) (one performed within one day prior to first dose of study treatment and the other performed during the screening period [Day -28 to Day -1]) in non-transfusion dependent (NTD) participants
  • •Adequate folate levels or on folate therapy
  • •Platelet count ≥100 x 10^9/L and ≤1,000 x 10^9/L
  • •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3 x upper limit of normal (ULN)
  • •Serum creatinine ≤ 1.5 x ULN
  • •Ejection fraction ≥50% by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA)

排除标准

  • •Discontinuation/withdrawal from study A536-04 due to participant request, participant unwillingness or inability to comply with the protocol, pregnancy, use of prohibited medication (e.g., hydroxyurea), medical reason or adverse event, hypersensitivity reaction to the study drug, at the discretion of the sponsor, or loss to follow-up prior to completion of the treatment period
  • •Any clinically significant pulmonary (including pulmonary hypertension), cardiovascular, endocrine, neurologic, hepatic, gastrointestinal, infectious, immunological (including clinically significant allo- or auto-immunization) or genitourinary disease considered by the investigator as not adequately controlled prior to the first dose of study trearment
  • •Symptomatic splenomegaly
  • •Splenectomy within 56 days prior to the first dose of study treatment
  • •Major surgery (except splenectomy) within 28 days prior to the first dose of study treatment. Participants must have completely recovered from any previous surgery prior to the first dose of study treatment
  • •Participants receiving or planning to receive hydroxyurea treatment. Participants must not have had hydroxyurea within 90 days of the first dose of study treatment
  • •For participants with treatment interruption: Iron chelation therapy if initiated within 56 days prior to the first dose of study treatment
  • •Cytotoxic agents, systemic corticosteroids, immunosuppressants, or anticoagulant therapy such as warfarin or heparin within 28 days prior to the first dose of study treatment (prophylactic aspirin up to 100 mg/day and low molecular weight (LMW) heparin for superficial vein thrombosis (SVT) is permitted)
  • •Treatment with another investigational drug (including sotatercept [ACE-011]) or device, or approved therapy for investigational use ≤28 days prior to the first dose of study treatment, or if the half-life of the previous investigational product is known, within 5 times the half-life prior to the first dose of study treatment, whichever is longer at any time between the end of treatment of the base study A536-04 and the first dose of study treatment
  • •Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B virus (HBV) or active infectious hepatitis C virus (HCV)
  • •Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥150 mm mercury (Hg) or diastolic blood pressure (DBP) ≥100 mm Hg
  • •Known history of thromboembolic events ≥Grade 3 according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0
  • •Pregnant or lactating females
  • •History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug

研究组 & 干预措施

Luspatercept Extension Population

Experimental

Participants receive luspatercept 0.6, 0.8, 1.0, or 1.25 mg/kg administered by subcutaneous injection on Day 1 of each 21-day cycle for up to 87 cycles (up to approximately 5 years). Participants will receive the highest tolerated dose level of luspatercept that they were assigned in the base study unless a dose modification was required.

干预措施: luspatercept (Drug)

结局指标

主要结局

Number of Participants Who Experienced an Adverse Event (AE)

时间窗: Up to approximately 68 months

An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which did not necessarily have a causal relationship with the treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. The number of participants who experienced an AE is reported.

Number of Participants Who Discontinued Study Treatment Due To an AE

时间窗: Up to approximately 60 months

An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which did not necessarily have a causal relationship with the treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. The number of participants who discontinued study treatment due to an AE is reported.

次要结局

  • Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline Over a Rolling 8-week Interval(Any 8-week interval during the study (up to approximately 68 months))
  • Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During Weeks 13 to 24(Weeks 13 to 24)
  • Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During Weeks 37 to 48(Weeks 37 to 48)
  • Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline Over a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During Weeks 13 to 24(Weeks 13 to 24)
  • Percentage of Transfusion Dependent (TD) Participants With a ≥33% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 8-Week Interval(Any 8-week interval during the study (up to approximately 68 months))
  • Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline Over a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline Over a Rolling 8-week Interval(Any 8-week interval during the study (up to approximately 68 months))
  • Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During Weeks 37 to 48(Weeks 37 to 48)
  • Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 8-week Interval(Any 8-week interval during the study (up to approximately 68 months))
  • Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 8-week Interval(Any 8-week interval during the study (up to approximately 68 months))
  • Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Percentage of Transfusion Dependent (TD) Participants With a ≥33% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-Week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During Weeks 13 to 24(Weeks 13 to 24)
  • Percentage of Transfusion Dependent (TD) Participants With a ≥33% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During Weeks 13 to 24(Weeks 13 to 24)
  • Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During Weeks 13 to 24(Weeks 13 to 24)
  • Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During Weeks 37 to 48(Weeks 37 to 48)
  • Percentage of Transfusion Dependent (TD) Participants With a ≥33% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During Weeks 37 to 48(Weeks 37 to 48)
  • Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During Weeks 37 to 48(Weeks 37 to 48)
  • Percentage of Transfusion Dependent (TD) Participants Who Maintained Red Blood Cell (RBC) Transfusion Independence For ≥8 Weeks(Any 8-week interval during the study (up to approximately 68 months))
  • Time To Erythroid Response for Transfusion Dependent (TD) Participants Who Achieved a Transfusion Burden Reduction of ≥33% Over a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Maximum Percent Change From Baseline in Red Blood Cell (RBC) Transfusions in Transfusion Dependent (TD) Participants Over 8 Weeks(Any 8-week interval during the study (up to approximately 68 months))
  • Maximum Percent Change From Baseline in Red Blood Cell (RBC) Transfusions in Transfusion Dependent (TD) Participants Over 12 Weeks(Any 12-week interval during the study (up to approximately 68 months))
  • Time To Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.0 g/dL Over a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Time To Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.5 g/dL Over a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Time To Erythroid Response for Transfusion Dependent (TD) Participants Who Achieved a Transfusion Burden Reduction of ≥50% Over a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Duration of Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.0 g/dL Over a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Duration of Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.5 g/dL Over a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Duration of Erythroid Response for Transfusion Dependent (TD) Participants Who Achieved a Transfusion Burden Reduction of ≥33% Over a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Duration of Erythroid Response for Transfusion Dependent (TD) Participants Who Achieved a Transfusion Burden Reduction of ≥50% Over a Rolling 12-week Interval(Any 12-week interval during the study (up to approximately 68 months))
  • Mean Change From Baseline in Pre-transfusion Hemoglobin Levels in Transfusion Dependent (TD) Participants(Any 8 or 12-week interval during the study (up to approximately 68 months))
  • Mean Change From Baseline in Hemoglobin Level Over Multiple Rolling 8-Week Intervals in Non-transfusion Dependent (NTD) Participants(Baseline (prior to first dose of study drug) and multiple 8-week intervals during the study (up to approximately 68 months))
  • Mean Change From Baseline in Hemoglobin Level Over Multiple Rolling 12-Week Intervals in Non-transfusion Dependent (NTD) Participants(Baseline (prior to first dose of study drug) and multiple 12-week intervals during the study (up to approximately 68 months))
  • Percent Change From Baseline in Transfusion Burden Over Multiple Rolling 8-Week Intervals in Transfusion Dependent (TD) Participants(Baseline (prior to first dose of study drug) and multiple 8-week intervals during the study (up to approximately 68 months))
  • Percent Change From Baseline to End of Treatment in Serum Ferritin(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline to End of Treatment in Percent Transferrin (Iron) Saturation(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline to End of Treatment in Serum Hepcidin(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline in Transfusion Burden Over Multiple Rolling 12-Week Intervals in Transfusion Dependent (TD) Participants(Baseline (prior to first dose of study drug) and multiple 12-week intervals during the study (up to approximately 68 months))
  • Percent Change From Baseline to End of Treatment in Reticulocyte Count(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline to End of Treatment in Soluble Transferrin Receptor(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline to End of Treatment in Non-transferrin Bound Iron (NTBI)(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Change From Baseline in Liver Iron Concentration (LIC) For Participants With Baseline LIC ≥3 mg/g Dry Weight Measured After 18 Months and Up to 60 Months of Treatment(Baseline (prior to first dose of study drug) and up to approximately 60 Months)
  • Change From Baseline in Liver Iron Concentration (LIC) For Participants With Baseline LIC <3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), Measured After 18 Months and Up to 60 Months of Treatment(Baseline (prior to first dose of study drug) and up to approximately 60 Months)
  • Change From Baseline in Liver Iron Concentration (LIC) For Participants With Baseline LIC ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), Measured After 18 Months and Up to 60 Months of Treatment(Baseline (prior to first dose of study drug) and up to approximately 60 Months)
  • Percent Change From Baseline to End of Treatment in Erythropoietin(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline to End of Treatment in Serum Iron(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline to End of Treatment in Indirect Bilirubin(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Change From Baseline in Liver Iron Concentration (LIC) For Participants With Baseline LIC ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), Measured After 18 Months and Up to 60 Months of Treatment(Baseline (prior to first dose of study drug) and up to approximately 60 Months)
  • Serum Concentration of Luspatercept(Predose and Postdose Days 1, 8, 22, 169, 176, 190, 337, and 344)
  • Percent Change From Baseline to End of Treatment in Nucleated Red Blood Cell (nRBC) Count(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline to End of Treatment in Lactate Dehydrogenase (LDH)(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline to End of Treatment in Serum Transferrin(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline to End of Treatment in Serum Total Iron Binding Capacity (TIBC)(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Percent Change From Baseline to End of Treatment in Total Bilirubin(Baseline (prior to first dose of study drug) and End of Treatment (up to Day 1807))
  • Change From Baseline in Liver Iron Concentration (LIC) For Participants With Baseline LIC <3 mg/g Dry Weight Measured After 18 Months and Up to 60 Months of Treatment(Baseline (prior to first dose of study drug) and up to approximately 60 Months)
  • Change From Baseline in Liver Iron Concentration (LIC) For Participants With Baseline LIC <3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), Measured After 18 Months and Up to 60 Months of Treatment(Baseline (prior to first dose of study drug) and up to approximately 60 Months)

研究者

发起方
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
申办方类型
Industry
责任方
Sponsor

研究点 (1)

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